Background and study aim: AFP is the most commonly utilized biomarker for HCC although it has a low sensitivity and specificity for the disease. New biomarkers with better sensitivity and specificity are to be studied. The aim of this work is to evaluate the role of midkine as a biomarker for early detection of HCC and for detection of HCC in patients negative for AFP. Patients and Methods: This study included 46 HCC patients on top of Child Pugh class A cirrhosis (group A), 46 patients with Child Pugh class A cirrhosis without liver focal lesion(s) (group B) and 46 apparently healthy controls (group C). Demographics, clinical data, radiologic findings, biochemical profile including serum AFP and midkine assessment using specific ELISA tests of the study participants were entered in the study. Results: Serum midkine had a statistically significant better sensitivity, specificity, positive predictive value, negative predictive value and accuracy over serum AFP for diagnosing very early and early HCC from liver cirrhosis and for diagnosing AFP negative HCC from liver cirrhosis. Conclusion: Serum midkine is to be considered for diagnosis of very early and early HCC especially in AFP negative cases.